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WO2014167969A1 - Méthode de détection du cancer du colon - Google Patents

Méthode de détection du cancer du colon Download PDF

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Publication number
WO2014167969A1
WO2014167969A1 PCT/JP2014/057588 JP2014057588W WO2014167969A1 WO 2014167969 A1 WO2014167969 A1 WO 2014167969A1 JP 2014057588 W JP2014057588 W JP 2014057588W WO 2014167969 A1 WO2014167969 A1 WO 2014167969A1
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Prior art keywords
monoclonal antibody
fragment
colorectal cancer
exosome
signal intensity
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PCT/JP2014/057588
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English (en)
Japanese (ja)
Inventor
英樹 太田
博之 岡本
園田　光
孝広 落合
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THEORIA SCIENCE Inc
Shionogi and Co Ltd
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THEORIA SCIENCE Inc
Shionogi and Co Ltd
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Publication date
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Priority to EP14782540.0A priority Critical patent/EP2985605A4/fr
Priority to US14/778,831 priority patent/US20160047812A1/en
Priority to CA2907606A priority patent/CA2907606A1/fr
Priority to CN201480019268.8A priority patent/CN105074468A/zh
Priority to JP2015511175A priority patent/JP6386995B2/ja
Publication of WO2014167969A1 publication Critical patent/WO2014167969A1/fr
Anticipated expiration legal-status Critical
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57419—Specifically defined cancers of colon
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705

Definitions

  • the present invention relates to a method for detecting colorectal cancer. More specifically, a method for detecting the presence of colorectal cancer using a monoclonal antibody against a specific antigen (CD9, CD63, CD147) on the exosome surface (CD9, CD63, CD147) in the sample or an antibody fragment thereof,
  • the present invention relates to methods for evaluating therapeutic effects and kits used in these methods.
  • Exosomes are vesicular granules that exist in body fluids in vivo. It is known that various membrane proteins exist on the exosome surface as in the general cell surface. In addition, exosomes have been reported to be secreted from various cells, such as cells of the immune system and various cancer cells, functioning as mediators of intercellular communication in vivo and related to physiological phenomena, Relevance to diseases such as cancer is drawing attention.
  • Non-Patent Document 1 reports that exosomes are isolated from the ascites and blood of ovarian cancer patients, and they are taken into immune system cells to suppress immunity, thereby increasing the tumor.
  • CD24, ADAM10, and CD9 antibodies are used for detection of exosomes.
  • Patent Document 1 discloses that various cancers are diagnosed using CD9, CD31, CD63, CD81, CD82, CD37, CD53, etc. as surface markers of vesicles existing in a living body.
  • Non-Patent Document 2 discloses that since HAb18G / CD147 is expressed in 28 types of cancer cells more than normal cells, a monoclonal antibody of the protein can be used as a tumor biomarker.
  • Non-Patent Document 3 reports that the expression of MAGE-1 and HER-2 / neu is increased in microvesicles present in the plasma of gastric cancer patients.
  • Non-Patent Document 4 discloses a cancer antigen diagnostic kit for measuring serum CA19-9.
  • Cancer can be detected using membrane proteins present in vesicle granules such as exosomes as biomarkers.
  • membrane proteins present in vesicle granules such as exosomes as biomarkers.
  • it is difficult to obtain sufficient results due to large fluctuations in sensitivity and specificity, etc., and it may be false positive in conventional cancer diagnosis
  • An object of the present invention is to provide a method for detecting colorectal cancer by measuring exosomes, and a kit used for the method.
  • the present invention relates to the following [1] to [7].
  • [1] A step of measuring the amount of exosomes expressing CD147 in a body fluid sample derived from a subject using an anti-CD147 monoclonal antibody or a fragment thereof; A step of comparing the signal intensity of the exosome in the step and the signal intensity in the control, wherein the signal intensity in the subject is recognized to be stronger than the signal intensity in the control, A method for detecting colorectal cancer.
  • a body fluid sample derived from a subject after treatment using at least one selected from the group consisting of an anti-CD9 monoclonal antibody and a fragment thereof, an anti-CD63 monoclonal antibody and a fragment thereof, and an anti-CD147 monoclonal antibody or a fragment thereof Measuring the amount of exosomes expressing CD9 and / or CD63 and CD147; Comparing the signal intensity of the exosome in said step with the signal intensity in the subject prior to treatment;
  • a method for evaluating colorectal cancer treatment comprising the step of evaluating that the treatment has a therapeutic effect on colorectal cancer when the signal strength after treatment is recognized to be weaker than the signal strength before treatment.
  • [5] For use in the method according to [2] or [3] above, which comprises an anti-CD9 monoclonal antibody and / or an anti-CD63 monoclonal antibody or a fragment thereof and an anti-CD147 monoclonal antibody or a fragment thereof.
  • Kit. Use of an exosome recognized as a marker for colon cancer by at least one selected from the group consisting of an anti-CD9 monoclonal antibody and a fragment thereof, an anti-CD63 monoclonal antibody and a fragment thereof, and the anti-CD147 monoclonal antibody or a fragment thereof .
  • an exosome recognized by at least one selected from the group consisting of an anti-CD9 monoclonal antibody and a fragment thereof, an anti-CD63 monoclonal antibody and a fragment thereof, and the anti-CD147 monoclonal antibody or a fragment thereof
  • a method for providing information on colorectal cancer or suspicion of colorectal cancer comprising detecting from
  • FIG. 1 is a diagram showing the results of proteome analysis using exosomes derived from human colon cancer cell line HCT116.
  • FIG. 2 is a diagram showing the results of CD147 detection by Western blotting. Each lane of 500 ng of exosome extract was run and detected using anti-CD147 mouse monoclonal antibody.
  • FIG. 3 is a diagram showing the detection results of CD147 in exosomes derived from colorectal cancer cell lines using the exoscreen method. Biotinylated antibody; CD147, acceptor bead binding antibody; CD9.
  • FIG. 4 is a diagram showing the detection result of CD147 in exosome derived from serum of colorectal cancer patients using the exoscreen method.
  • FIG. 5 is a diagram showing the detection result of CD147 in exosome derived from serum of colorectal cancer patients using the exoscreen method. Biotinylated antibody; CD147, acceptor bead binding antibody; CD9.
  • FIG. 6 is a graph comparing the detection results of exosome-derived CD147, CEA, and CA19-9 in colorectal cancer patient serum.
  • FIG. 7A is a diagram showing the results of ROC analysis when colorectal cancer was diagnosed using exosome-derived CD147 as an index (FIG. 5).
  • FIG. 5 is a diagram showing the results of ROC analysis when colorectal cancer was diagnosed using exosome-derived CD147 as an index (FIG. 5).
  • FIG. 7B is a diagram showing a result of ROC analysis when colorectal cancer is diagnosed using CEA as an index.
  • FIG. 7C is a diagram showing a result of ROC analysis when colorectal cancer is diagnosed using CA19-9 as an index.
  • FIG. 8 is a diagram showing the detection results of CD147 in exosomes derived from serum of colorectal cancer patients before and after surgery using the exoscreen method. The line at the center of each data indicates the median value of the detection results.
  • the present invention is a method for detecting colorectal cancer in a subject, wherein a signal derived from an exosome in a body fluid sample is measured using a specific monoclonal antibody, and the value is larger than that of a healthy person.
  • the main feature is that it is judged that the patient may have cancer.
  • a step of measuring the amount of exosome expressing the antigen in a body fluid sample derived from a subject (hereinafter also referred to as step A)
  • a step of comparing the signal intensity of the exosome and the signal intensity in the control (hereinafter also referred to as process B), where the signal intensity in the subject is recognized to be stronger than the signal intensity in the control, It is an indicator of the presence of colorectal cancer.
  • detecting colorectal cancer includes detecting the onset of colorectal cancer and the degree of progression of the disease state.
  • a measurement system comprising a combination of an anti-CD9 antibody and an anti-CD63 antibody can obtain a stronger signal intensity in the blood of a colorectal cancer patient than in the blood of a healthy person.
  • a strong signal is detected to some extent, and there is a problem as a diagnostic method for colorectal cancer.
  • CD147 was successfully identified as an antigen specific to exosomes secreted from colon cancer cells with high malignancy from proteomic analysis of colon cancer cell lines.
  • Step A is a step of measuring the amount of exosomes expressing the antigen in a body fluid sample derived from a subject using a monoclonal antibody or a fragment thereof against the specific antigen.
  • Examples of the monoclonal antibody or fragment thereof used in Step A include three types of monoclonal antibodies or fragments thereof. Specifically, an anti-CD147 monoclonal antibody or a fragment thereof, an anti-CD9 monoclonal antibody or a fragment thereof, an anti-CD63 monoclonal antibody or a fragment thereof, and at least an anti-CD147 monoclonal antibody or a fragment thereof is used.
  • the monoclonal antibody or fragment thereof used in the present invention may be any antibody that recognizes a specific antigen, and can be prepared according to a known method. That is, an anti-CD147 monoclonal antibody or a fragment thereof recognizes CD147, an anti-CD9 monoclonal antibody or a fragment thereof recognizes CD9, and an anti-CD63 monoclonal antibody or a fragment thereof recognizes CD63. It may be prepared or may be prepared based on sequence information of each antigen.
  • the anti-CD9 monoclonal antibody and the anti-CD63 monoclonal antibody as a hybridoma producing the monoclonal antibody, the National Institute of Technology and Evaluation, National Institute of Technology and Technology (1-1-1 Tsukuba, Tsukuba City, Ibaraki Prefecture) Those obtained from cells deposited at the center center 6) under the following deposit number can also be used.
  • FERM BP-11519 (monoclonal antibody produced is CD9-12A12 antibody, designated CD9: 12A12, date of acceptance November 8, 2011)
  • FERM BP-11520 (monoclonal antibody produced is CD63-8A12 antibody, designated CD63: 8A12, date of acceptance November 8, 2011)
  • FERM BP-11521 (the monoclonal antibody produced is the CD63-13C8 antibody, designated CD63: 13C8, date of commissioning November 8, 2011)
  • the “monoclonal antibody fragment” means a fragment that is a part of the above-described monoclonal antibody and has a specific binding property to CD9, CD63, or CD147 in the same manner as the monoclonal antibody.
  • the fragment having specific binding property to CD9, CD63 or CD147 is Fab, F (ab ′) 2 , Fab ′, single chain antibody (scFv), disulfide stabilized antibody (dsFv) Examples include dimerized V region fragments (Diabodies), peptides containing CDRs, etc. (Expert Opinion on Therapeutic Patents, Vol. 6, No. 5, pp. 441-456, 1996) ).
  • Aspect 1 Use of anti-CD147 monoclonal antibody or fragment thereof
  • Aspect 2 Anti-CD9 monoclonal antibody and fragment thereof, at least one selected from the group consisting of anti-CD63 monoclonal antibody or fragment thereof, and anti-CD147 monoclonal antibody or fragment thereof Aspect used in combination
  • the exosome expressing CD147 can be quantified by recognizing it with an anti-CD147 monoclonal antibody labeled with CD147 on exosome or a fragment thereof.
  • the labeling of the anti-CD147 monoclonal antibody or a fragment thereof is not particularly limited and can be performed according to a known method.
  • the monoclonal antibody of Embodiment 1 or a fragment thereof is suitably used for the Western blot method described later.
  • CD9 and / or CD63 and CD147 on exosomes are recognized by these monoclonal antibodies or fragments thereof, and exosomes expressing CD9 and / or CD63 and CD147 can be quantified.
  • the anti-CD147 monoclonal antibody or a fragment thereof may be used as a solid phase antibody, and the anti-CD9 monoclonal antibody or a fragment thereof may be used as a labeled antibody.
  • an anti-CD9 monoclonal antibody or a fragment thereof may be used as a solid phase antibody, and an anti-CD147 monoclonal antibody or a fragment thereof may be used as a labeled antibody.
  • an anti-CD63 monoclonal antibody or a fragment thereof may be used as a solid phase antibody, and an anti-CD147 monoclonal antibody or a fragment thereof may be used as a labeled antibody.
  • an anti-CD63 monoclonal antibody or a fragment thereof may be used as a labeled antibody, and an anti-CD147 monoclonal antibody or a fragment thereof may be used as a solid phase antibody.
  • an anti-CD9 monoclonal antibody or a fragment thereof and an anti-CD63 monoclonal antibody or a fragment thereof may be used as a solid phase antibody, and an anti-CD147 monoclonal antibody or a fragment thereof may be used as a labeled antibody.
  • an anti-CD9 monoclonal antibody or a fragment thereof and an anti-CD63 monoclonal antibody or a fragment thereof may be used as a labeled antibody
  • an anti-CD147 monoclonal antibody or a fragment thereof may be used as a solid phase antibody.
  • the preparation of the solid phase antibody and the labeled antibody is not particularly limited and can be performed according to a known method.
  • the monoclonal antibody of Embodiment 2 or a fragment thereof is suitably used in the sandwich ELISA method and exoscreen method described later.
  • the sample used for measuring the amount of exosome is not limited as long as it is a body fluid sample, and is selected from the group consisting of blood, serum, plasma, urine, saliva, milk, nasal discharge, cerebrospinal fluid, for example. What is done is illustrated.
  • the exosome amount may be measured by any method using the monoclonal antibody or a fragment thereof, and can be performed, for example, according to the Western blot method, sandwich ELISA method, or exoscreen method.
  • the monoclonal antibody of Aspect 1 or a fragment thereof can be used.
  • CD147 present on exosomes derived from colorectal cancer cells can be detected by analyzing the blood of colorectal cancer patients by Western blotting using an anti-CD147 monoclonal antibody or a fragment thereof. .
  • the monoclonal antibody of Aspect 2 or a fragment thereof can be used. Specifically, first, one type of monoclonal antibody or a fragment thereof is used as a solid phase antibody, and a complex is formed by contacting with a sample containing exosomes. After that, another monoclonal antibody or a fragment thereof is added after labeling to form a further complex to detect the label, thereby measuring the amount of exosome expressing the antigen recognized by both antibodies. Can do.
  • the exoscreen method is an application of AlphaLISA developed by PerkinElmer.
  • two types of antibodies having different epitopes are used, one antibody is biotinylated, and the other is reacted with an analysis sample using an antibody to which Alpha LISA acceptor beads are bound. Thereafter, by adding donor beads to which streptavidin is bound, the biotinylated antibody and donor beads are bound via streptavidin, and the acceptor beads and donor beads are adjacent to each other.
  • the adjacent state within 200 nm
  • singlet oxygen is generated from the donor bead by excitation at 680 nm, and when singlet oxygen reaches the acceptor bead, light of 615 nm can be emitted and detected as a signal.
  • the amount of exosome containing the target protein in the body fluid sample can be measured.
  • the following step B is performed using the obtained exosome amount.
  • Step B is a step of comparing the signal intensity of the exosome obtained in Step A with the signal intensity in the control person.
  • the control person may be any person who does not develop colorectal cancer, and includes a healthy person.
  • the signal intensity in the control person is the exosome amount in the body fluid sample derived from the control person, and may be measured together with the measurement of the exosome amount of the subject in Step A or may be measured separately. Moreover, the exosome amount of a plurality of controls may be measured, and the exosome amount of the control may be set from the statistics.
  • the body fluid sample derived from the control is preferably a sample of the same type as the body fluid sample derived from the subject.
  • the body fluid sample derived from the control is also blood.
  • an anti-CD9 monoclonal antibody and its Exosomes recognized by at least one selected from the group consisting of a fragment, an anti-CD63 monoclonal antibody and a fragment thereof, and an anti-CD147 monoclonal antibody or a fragment thereof are detected from a body fluid sample derived from a subject, A method of providing information on colorectal cancer or suspected colorectal cancer can be mentioned.
  • the amount of exosomes after the operation is reduced by setting the amount of exosomes of the control to the amount of exosomes before the operation of the subject and comparing the amount of exosomes after the operation as the amount of exosomes of the subject. If is indicated, it can be determined that there is a high possibility that colorectal cancer is shrinking or decreasing.
  • the amount of exosome of the control person is set to the amount of exosome before treatment of the subject, and the amount of exosome after treatment is set as the amount of exosome of the subject.
  • the present invention also measures an exosome-derived signal using the monoclonal antibody or a fragment thereof before and after receiving colorectal cancer treatment, and the value after treatment is smaller than that before treatment. Furthermore, it is possible to provide an evaluation method characterized by determining that the treatment has an effect.
  • kits for detecting colorectal cancer are provided.
  • the kit of the present invention includes any kit that can detect exosomes in a body fluid sample.
  • a kit containing an antibody capable of recognizing an antigen present on the exosome surface that is, an anti-CD147 monoclonal antibody or a fragment thereof, an anti-CD9 monoclonal antibody or a fragment thereof, or an anti-CD63 monoclonal antibody or a fragment thereof can be mentioned.
  • Aspect 1 Aspect containing anti-CD147 monoclonal antibody or fragment thereof
  • Aspect 2 Anti-CD9 monoclonal antibody and fragment thereof, at least one selected from the group consisting of anti-CD63 monoclonal antibody or fragment thereof, and anti-CD147 monoclonal antibody or fragment thereof The aspect which contains in combination is mentioned.
  • kits can be used as long as they are detection methods using an antibody when detecting exosomes in a body fluid sample (for example, Western blot method, ELISA method, exoscreen method, etc.). If exosomes are detected, proteins other than exosomes may be detected simultaneously by the antibody.
  • kit of the present invention for example, when the amount of exosomes present in blood samples of healthy subjects and subjects is measured, and there is a significant difference between the expression levels of both, Decisions and / or diagnoses can be made.
  • FIG. 1 shows the results of proteome analysis using exosomes derived from the human colon cancer cell line HCT116 (American Type Culture Collection).
  • the antigen CD147 extracted from this result was evaluated for expression in the exosome derived from a colon cancer cell line by Western blotting using a mouse anti-human CD147 monoclonal antibody (manufactured by Novus Biologicals, clone MEM-M6 / 1).
  • human colorectal cancer cell lines HCT116 cells with very high malignancy and Caco2 cells (American Type Culture Collection) with low malignancy were compared.
  • the presence of CD147 could be confirmed in exosomes derived from the high-grade HCT116 cell line, and was not detected in exosomes derived from the low-grade Caco2 cells (FIG. 2).
  • an anti-CD9 monoclonal antibody (accession number FERM BP-11519) in which a biotinylated anti-CD147 monoclonal antibody (manufactured by Novus Biologics, clone MEM-M6 / 1) and acceptor beads are bound (accession number FERM BP-11519) is produced.
  • Signal from exosomes expressing CD9 and CD147 derived from each colorectal cancer cell line was measured by exoscreen method.
  • the expression of CD147 in exosomes derived from the high-grade HCT116 cell line was confirmed (FIG. 3), similar to the results by Western blotting. From these results, it is speculated that some colon cancer cells secrete many exosomes expressing CD147.
  • Test Example 2 Detection of exosomes derived from serum of colorectal cancer patients using CD147 antibody 1 Signal intensity derived from exosomes expressing CD9 or CD63 in 5 ⁇ L of colorectal cancer patient serum and expressing CD147 was detected by the exoscreen method.
  • an anti-CD63 monoclonal antibody in which the biotinylated anti-CD147 monoclonal antibody used in Test Example 1 and an acceptor bead are bound (monoclonal antibody produced by a hybridoma deposited under accession number FERM BP-11520) or The above-mentioned anti-CD9 monoclonal antibody bound with acceptor beads was used.
  • Test Example 3 Detection of exosomes derived from serum of colorectal cancer patients using CD147 antibody 2
  • signals derived from exosomes expressing CD9 and CD147 were measured using more serum from colorectal cancer patients and serum from healthy individuals (FIG. 5). Specifically, 194 sera from colon cancer patients and 191 sera from healthy individuals were used.
  • CEA and CA19-9 were measured on the same 194 sera as those derived from colon cancer patients whose exosome-derived signals were measured as described above.
  • the measurement results of CEA and CA19-9 and the results of measuring the signals derived from exosomes expressing CD9 and CD147 by the exoscreen method are shown together in FIG.
  • FIG. 7A, FIG. 7B, and FIG. 7C show ROC analysis and compare the detection ability of colorectal cancer of each measurement method, and the closer the AUC is to 1, the higher the detection ability.
  • AUC was found to be 0.820, much larger than that of CEA and CA19-9 (0.669 and 0.622, respectively) did.
  • Examination of colorectal cancer using signals derived from exosomes expressing CD9 and CD147 was shown to be superior to CEA and CA19-9.
  • Test Example 4 Analysis of changes in signal intensity before and after surgery
  • Changes in signals derived from exosomes expressing CD9 and CD147 before and after surgery were examined using sera from 15 patients undergoing Stage I and II colorectal cancer resection (FIG. 8).
  • Tests using signals derived from exosomes expressing CD9 and CD147 were found to be excellent as follow-up tests after surgery and drug administration.
  • the method of the present invention makes it possible to determine whether or not the sample provider has a high possibility of developing colorectal cancer. This is useful because the sample provider can take measures to prevent the progression of cancer.

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Abstract

La présente invention concerne une méthode de détection du cancer du colon comprenant une étape consistant à utiliser un anticorps monoclonal anti-CD147 ou un fragment de celui-ci et à quantifier les exosomes exprimant le CD147 dans un exemple de liquide corporel prélevé chez un sujet test, et une étape consistant à comparer la force du signal des exosomes de l'étape précédente avec la force du signal d'un sujet de référence, lors de laquelle, au cas où la force du signal du sujet test est plus grande que la force du signal du sujet de référence, ce résultat est interprété comme un indice de cancer du colon. Selon la méthode de la présente invention, il est possible de déterminer si un donneur d'échantillon est susceptible de souffrir d'un cancer du colon. En se basant sur ce résultat, des mesures peuvent être prises pour empêcher la progression du cancer chez le donneur d'échantillon et, par conséquent, la méthode selon la présente invention est très utile.
PCT/JP2014/057588 2013-04-08 2014-03-19 Méthode de détection du cancer du colon Ceased WO2014167969A1 (fr)

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EP14782540.0A EP2985605A4 (fr) 2013-04-08 2014-03-19 Méthode de détection du cancer du colon
US14/778,831 US20160047812A1 (en) 2013-04-08 2014-03-19 Method for detecting colon cancer
CA2907606A CA2907606A1 (fr) 2013-04-08 2014-03-19 Methode de detection du cancer du colon
CN201480019268.8A CN105074468A (zh) 2013-04-08 2014-03-19 大肠癌的检测方法
JP2015511175A JP6386995B2 (ja) 2013-04-08 2014-03-19 大腸がんの検出方法

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JP2013-080303 2013-04-08

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WO2018030511A1 (fr) * 2016-08-12 2018-02-15 公立大学法人和歌山県立医科大学 Procédé de détection de protéine présente dans une membrane d'exosomes
WO2018131192A1 (fr) 2017-01-12 2018-07-19 国立研究開発法人国立がん研究センター Procédé d'examen de la possibilité pour un sujet de souffrir d'un cancer du pancréas
JP2019527343A (ja) * 2016-06-21 2019-09-26 ナント ホールディングス アイピー エルエルシーＮａｎｔ Ｈｏｌｄｉｎｇｓ ＩＰ， ＬＬＣ 癌のエキソソーム誘導治療
JPWO2021045189A1 (fr) * 2019-09-05 2021-03-11
JP2022160422A (ja) * 2016-11-16 2022-10-19 ナノソミックス・インコーポレイテッド エキソソームの亜集団の定量および神経変性障害の診断

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US11243215B2 (en) 2016-01-14 2022-02-08 The Regents Of The University Of California 3D-exoquant method for the analysis of surface molecules and quantification of tissue-specific exosomes in biological fluids
US12392776B2 (en) * 2020-06-01 2025-08-19 City University Of Hong Kong Methods and kits for detecting exosomal protein

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EP2985605A4 (fr) 2017-02-15
JP6386995B2 (ja) 2018-09-05
JPWO2014167969A1 (ja) 2017-02-16
US20160047812A1 (en) 2016-02-18
CA2907606A1 (fr) 2014-10-16
CN105074468A (zh) 2015-11-18

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